1458 - Uncharted territories: applying “precision medicine” to understand the treacherous landscape of extensively and multidrug resistant (XDR and MDR) Pseudomonas aeruginosa in a patient with cystic fibrosis and lung transplantation

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Presenting Author(s)

LR

Laura J. Rojas

Postdoctoral Scholar
Case Western Reserve University
Cleveland, Ohio
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.

Co-Author(s)

Mohamad Yasmin

Doctor
Louis Stokes Cleveland VAMC
Cleveland, Ohio
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
JB

Jacquelynn Benjamino

Postdoctoral Associate
The Jackson Laboratory for Genomic Medicine
Farmington, CT
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
SM

Steven Marshall

MS
Louis Stokes Cleveland VA
Cleveland, Ohio
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
KD

Kailynn Deronde

Clinical Hospital Pharmacist - Pediatric/Adult Infectious Disease and Antimicrobial Stewardship
Jackson Memorial Hospital
Miami, Florida
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
NK

Nikhil Krishnan

Student
Case Western Reserve University School of Medicine
Cleveland, OH
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
FP

Federico Perez

Associate Professor of Medicine
Case Western Reserve University
Cleveland, OH
Disclosure: Accelerate (Research Grant or Support)Merck (Research Grant or Support)Pfizer (Research Grant or Support)
AC

Andrew Colin

Pediatric Pulmonology Specialist
University of Miami Health System
Miami, Florida
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
MC

Monica Cardenas

Pediatric Pulmonology Specialist
University of Miami Health System
Miami, Florida
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
OM

Octavio Martinez

Research Associate Professor
University of Miami Miller School of Medicine
Miami, Florida
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
AP

Armando Perez-Cardona

BS
Jackson Memorial Hospital
Miami, Florida
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
DR

Daniel Rhoads

Assistant Professor
Case Western Reserve University School of Medicine
Cleveland, Ohio
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
MJ

Michael R. Jacobs

Director, Medical Microbiology
Case Western Reserve University
Cleveland, Ohio
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
JS

Jacob Scott

Physician-Scientist
Cleveland Clinic
Cleveland, Ohio
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
MA

Mark D. Adams

Investigator
AMR
Lexington, Kentucky
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
Lilian M. Abbo

Professor of Infectious Diseases; Associate Chief Medical Officer in Infectious Diseases
University of Miami Miller School of Medicine, Miami Transplant Institute and Jackson Health System
Miami, FL
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
Robert A. Bonomo

Associate Chief of Staff for Academic Affairs
Case Western Reserve University/ Louis Stokes Cleveland VA Medical Center
Cleveland, OH
Disclosure: Entasis, Merck, Venatorx (Research Grant or Support)

Background: Pseudomonas aeruginosa is a persistent and difficult-to-treat pathogen in many patients, especially those with cystic fibrosis (CF). Herein, we describe our experience managing a young woman suffering from CF with XDR P. aeruginosa who underwent lung transplantation. We highlight the contemporary difficulties reconciling the clinical, microbiological, and genetic information.

Methods: Mechanism-based-susceptibility disk diffusion synergy testing with double and triple antibiotic combinations aided in choosing tailored antimicrobial combinations to control the infection in the pre-transplant period, create an effective perioperative prophylaxis regimen, and manage recurrent infections in the post-transplant period. Thirty-six sequential XDR and PDR P. aeruginosa isolates obtained from the patient within a 17-month period, before and after a double-lung transplant were analyzed by whole genome sequencing (WGS) and RNAseq in order to understand the genetic basis of the observed resistance phenotypes, establish the genomic population diversity, and define the nature of sequence changes over time

Results: Our phylogenetic reconstruction demonstrates that these isolates represent a genotypically and phenotypically heterogeneous population. The pattern of mutation accumulation and variation of gene expression suggests that a group of closely related strains was present in the patient prior to transplantation and continued to evolve throughout the course of treatment regardless of antibiotic usage.Our findings challenge antimicrobial stewardship programs that assist with the selection and duration of antibiotic regimens in critically ill and immunocompromised patients based on single-isolate laboratory-derived resistant profiles. We propose that an approach sampling the population of pathogens present in a clinical sample instead of single colonies be applied instead when dealing with XDR P. aeruginosa, especially in patients with CF.

Conclusion: In complex cases such as this, real-time combination testing and genomic/transcriptomic data could lead to the application of true “precision medicine” by helping clinicians choose the combination antimicrobial therapy most likely to be successful against a population of MDR pathogens present.